The major objective of this renewal project is to determine the public health significance of the chronic perinatal infection (cytomegalovirus-CMV, herpes simplex virus - HSV, rubella virus, Toxoplasma gondii and Treponema pallidum) through both prespective and retrospective, longitudinal studies of young pregnant women and their offspring. In this 5 year segment, particular emphasis will be placed on assessing the subclinical infections produced by CMV since they are far more prevalent than the others. CMV infections in the mother and baby will be proven by large virologic and serologic monitoring and immunologic screening for fetal antibody production. Longitudinal studies on long term outcome with respect to the development of chronic disease (especially with congenitally and natally acquired CMV) will be determined by serial clinical investigations and related quantitatively to viral persistence and the host response (B and T cell functions). In addition, investigations into the pathogenesis of CMV infections in the mother and baby will be undertaken. In the mother these will include studies on: the role of recurrent vs. primary infection as a cause for congenital and natal acquisitions and their relative effect on clinical outcome, the relation between antibody production and T cell activity with recurrent infections and the possible suppressor activity on viral production of chorionicgonadotropin in early gestation. In the infant and child with intrauterine and natally acquired CMV the following will be assessed: the relative roles of viral replication and immune complex formation as cause(s) for organ dysfunction, the nature of immune complex formation and its persistance, the dynamics of B and T cell activity in congenital and natal CMV in relation to the development of disease. Finally, the antigenic and genetic relatedness of CMV strains will be assessed to determine if maternal recurrences are due to reactivation of latent virus or reinfection by new strains, and whether severe fetal disease as opposed to low grade infection might be caused by varying virulence between strains.